The following are key points to remember from this practical guide on the use of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) from the European Heart Rhythm Association (EHRA):

1. Use of NOACs is contraindicated for AF patients with mechanical prosthetic valves or moderate-severe mitral stenosis (usually of rheumatic origin). Although there are limited data for patients with bioprosthetic valves, mitral valve repair, or transcatheter aortic valve replacement, use is acceptable.
2. Structured follow-up is recommended for patients on chronic NOAC use. This includes documentation of anticoagulation indication, checking baseline laboratory studies (hemoglobin, renal and liver function, coagulation panel), providing education, and coordinating follow-up with at least once-yearly laboratory studies. Repeat laboratory testing should be performed more frequently for patients with baseline renal dysfunction or the elderly.
3. It is important to calculate renal function using the Cockcroft-Gault equation. This is used to appropriately dose NOACs. Use of NOACs is not recommended for patients with creatinine clearance <15-30 ml/min or on dialysis. Note: In the United States, apixaban is dosed based on serum creatinine level, weight, and age (this differs from European dosing). Also, both apixaban and rivaroxaban are Food and Drug Administration (FDA) approved for use with dialysis.
4. It is also important to check baseline liver function before starting NOACs. NOACs are contraindicated for patients with Child-Pugh category C hepatic insufficiency. Rivaroxaban is also contraindicated in Child-Pugh category B hepatic insufficiency.
5. When switching from warfarin to a NOAC, the NOAC should be started when the international normalized ratio (INR) is <2.5. When switching from a NOAC to warfarin, warfarin should be started and the NOAC continued until the INR is ≥2. Repeat the INR 1-3 days after stopping NOAC to ensure INR remains therapeutic.
6. Although NOACs have fewer drug-drug interactions than warfarin, there are still important drug-drug interactions to monitor. These include the P-glycoprotein and CYP3A4 interacting medicines. Important examples include avoiding concurrent use of dronedarone, rifampin, many HIV protease inhibitors, itraconazole, ketoconazole, voriconazole, St. John’s wort, and dexamethasone.
7. In the case of a nonlife-threatening major bleeding event, plasma levels of NOACs should normalize within 12-24 hours for patients with normal renal function. It may take longer for patients with renal insufficiency, particularly for dabigatran.
8. In the case of a life-threatening major bleeding event, patients on dabigatran can be given idarucizumab 5 mg IV in two doses no more than 15 minutes apart. Patients taking factor Xa inhibitors should be given prothrombin complex concentrate 50 U/kg. All patients should receive supportive measures, including mechanical compression and endoscopic or surgical hemostasis (if applicable).
9. Following a major gastrointestinal bleeding event, NOACs should be restarted as early as feasible (usually 4-7 days) if the risk of stroke persists and outweighs the risk of recurrent bleeding.
10. Most patients taking NOACs can safely undergo surgical procedures with a 24- to 48-hour pre-procedure hold. Longer hold times may be necessary for patients taking dabigatran who have chronic kidney disease. No bridging heparin is needed for NOAC-treated patients. Resume full-dose NOAC within 72 hours post-procedure, once the bleeding risk is appropriate.
11. For patients taking NOAC who present with an acute coronary syndrome, primary percutaneous coronary intervention (PCI) can be performed (preferably using a radial approach) emergently for ST-segment elevation myocardial infarction (STEMI) patients or delayed for 24-48 hours in stable NSTEMI patients. Consider a proton pump inhibitor for patients taking combined NOAC with antiplatelet medications.
12. For patients taking NOAC with single or dual antiplatelet therapy, shorter courses of antiplatelets are recommended. Patients with elective PCI may benefit from dual therapy (NOAC plus clopidogrel from discharge through 1 year). Patients with acute coronary syndromes who undergo PCI should receive triple therapy for up to 3 months, then switch to dual therapy (NOAC plus clopidogrel) until 1 year. After 1 year, all patients should continue on NOAC monotherapy.
13. For patients taking NOAC who present with an acute ischemic stroke, proceed with thrombolysis if the NOAC plasma level is below the lower limit of detection or if the last intake was >48 hours prior and renal function is normal. Otherwise consider thrombolysis in select patients after NOAC reversal or use of endovascular therapy.
14. For patients taking NOACs who present with an acute ischemic stroke, consider re-starting NOACs after 3-14 days, depending on the degree of neurologic deficit and excluding any hemorrhagic transformation on brain computed tomography.

Keywords: Acute Coronary Syndrome, Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Blood Coagulation Factors, Brain Ischemia, Creatinine, Cytochrome P-450 CYP3A, Factor Xa Inhibitors, Hemoglobins, Heart Failure, Hemorrhage, Geriatrics, Mitral Valve Stenosis, Myocardial Ischemia, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Primary Prevention, Renal Dialysis, Renal Insufficiency, Chronic, Stroke, Tomography, X-Ray Computed, Transcatheter Aortic Valve Replacement, Vascular Diseases, Warfarin

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